Bill is a 13 year old boy who is tested for Haemochromatosis on a background of his parent being a homozygous C282Y carrier.
Results show
C282Y * – Heterozygous Mutation Detected
H63D – Mutation Not Detected
Questions
- What are the genes commonly tested for?
- What are the complications of haemochromatosis?
- What do you tell the patient about the implications of this result?
- Does this patient need treatment?
- What is the likelihood of this patient passing this gene onto their offspring?
- What is the management of full haemochromatosis?
Risks of Mutations
| Genetic test result | Explanation | Risk of iron overload | How many Caucasian Australians have this genotype? |
|---|---|---|---|
| Homozygous C282Y | 2 copies of the C282Y mutation | Greatly increased risk | 1 in 200 |
| Compound heterozygous C282Y / H63D | 1 copy of C282Y mutation and 1 copy of H63D mutation | Increased risk | 1 in 50 |
| Homozygous H63D | 2 copies of H63D mutation | Very slightly increased risk | 1 in 100 |
| Heterozygous H63D | 1 copy of H63D mutation and one normal gene | Probably no increased risk | 1 in 5 |
| Heterozygous C282Y | 1 copy of C282Y mutation and one normal gene | Probably no increased risk | 1 in 9 |
| Normal genotype | No mutations detected | No increased risk | 2 in 3 |
Autosomal Recessive Disorder
Haemochromatosis is a recessive gene disorder. That means for the condition to be passed on, both mother and father must have one copy of the abnormal HFE gene. About one in seven people have one abnormal HFE gene. They are referred to as a ‘carrier’ because they carry a gene which may cause their children to inherit the disorder. Carriers won’t develop the condition themselves.
If two carriers have children, their child has:
• a 50 per cent chance of inheriting one mutated HFE gene and becoming a carrier
• a 25 per cent chance of inheriting both mutated HFE genes and therefore being at risk of excess iron absorption and developing symptoms of haemochromatosis
• a 25 per cent chance of inheriting two normal genes.
Heterozygous:
Having one copy of the abnormal HFE gene, for example C282Y or H63D – also known as a ‘carrier’.
Homozygous:
Two copies of the same gene abnormality, for example C282Y and C282Y.
Compound heterozygous:
Having one C282Y and one H63D abnormal gene. Compound heterozygotes usually have a milder form of haemochromatosis.
References
